ABSTRACT Acute painful vasocclusive crises (VOC) are the most common reason for emergency department (ED) visits and hospitalizations for patients with sickle cell disease. NHLBI guidelines and evidence based recommendations in sickle cell disease exist to ensure that high quality care is provided to patients to both treat and prevent these crises. However, guideline based care to prevent VOC and ensure timely treatment of acute VOC in EDs is infrequently followed and results in both more frequent and prolonged pain. Current evidence supports using hydroxurea for eligible patients to prevent the occurrence of painful VOC. However, hydroxyurea continues to be underutilized in eligible patients despite widespread efforts to increase its use. In addition, for patients who present to the ED with acute VOC, guidelines provide best practice recommendations to initiate the first dose of opioid within 30 minutes of triage and subsequent reassessment and retreatment every 15-30 minutes until pain is under control. Prior work by our study team and others demonstrate that we fail to meet guidelines for timeliness in opioid administration and that using an intranasal route of opioid administration may improve timeliness and may be associated with lower admission rates to the hospital. Children presenting to the ED for painful crises represent a high risk population that would benefit from timely acute care. In addition, knowing hydroxyurea is underutilized, we intend to use these acute care visits to the ED as an opportunity to identify patients who should be receiving hydroxyurea long term to prevent these painful VOC. We propose to leverage the data capabilities and sickle cell experience of the Pediatric Emergency Care Applied Research Network (PECARN) to better understand the barriers and facilitators to guideline adherent sickle cell disease care and develop interventions to improve guideline adherent care. We will utilize the multicenter clinical data repository of electronic health record data (the PECARN registry) to conduct implementation research in a rapid cycle manner to improve the acute care of children with sickle cell disease. The PECARN has already successfully conducted a multicenter randomized trial of a therapeutic intended to decrease hospital length of stay for pain in children with sickle cell disease. Additionally, PECARN registry sites have used the data registry to improve the timeliness of care for children with asthma. Data that is already collected directly from the electronic health record in the PECARN registry encompasses over 2.4 million pediatric ED visits, with approximately 4,000 visits for children with sickle cell VOC annually added to the registry. Our long-term goal is to improve the care of children with painful complications of SCD through both quality improvement and research. Our overall hypothesis is we will successfully identify the barriers and facilitators to NHLBI guideline adherent care for pain in SCD, allowing for the design of a successful multi- center hybrid effectiveness-implementation trial to improve the experience of children with SCD when they present in acute pain.